Individuals suffer from skin wounds from time to time, and typically, such wounds of a healthy individual would recover within an expected time frame. However, for individuals suffering from burn injuries, trauma, immobility and/or diseases (e.g., diabetics), skin wounds tend to become chronic wounds, which are defined as wounds that do not heal in an expected time frame based on the patient's age, wound location, wound size or wound etiology. Chronic wounds often leave patients at risk for infection, hospitalization and potential amputation of infected limbs, and are becoming a major public health concern. Chronic wounds lead to high rates of morbidity and mortality, diminished quality of life and high healthcare costs. Ideally, conventional wound therapy would result in healing, eliminating the occurrence of chronic wounds, and the need of further intervention. However, in the event of non-healing wounds, more aggressive forms of therapy to promote wound healing, such as application of bio-synthetic dressings, skin substitutes or administration of growth factors, is adopted.
Tissue-engineered skin substitutes (i.e., human skin equivalents) have been developed as products that use living cells (e.g., keratinocytes and fibroblasts) in a scaffold of natural, biodegradable or synthetic matrices to foster wound healing. The scaffold provides a stable framework that guides tissue integration and development. It becomes coated with proteins and lipids, influencing cell migration and adherence. Skin substitutes, also called artificial skin or cellular wound dressings, may be used as temporary or permanent wound coverings, or in conjunction with conventional wound therapy. Some substitutes have a synthetic top layer that eventually peels away or is replaced by new, healthy skin. The bottom layer is composed of a scaffold or matrix, and supports and promotes new cell growth. As the healthy skin, blood vessels, fibroblasts and nerve fibers cross into the matrix, it eventually degrades and disappears. Most commercial available skin substitutes are consisted of sheets of biomaterial matrix with or without allogenic cells contained thereon, which are typically derived from neonatal foreskin; such products include, for example, Alloderm® (Life Cell Inc., Branchburg, N.J.), Integra® (Integra LifeSciences corp., Plainsboro, N.J.), EZ Derm™ (Brennen Medical, Inc., St. Paul, Minn.), Dermagraft® (Smith & Nephew, Inc., Largo, Fla.), Oasis® (Cook Biotech Inc., West Lafayette, Ind.), Apligraft®(Organogenessis, Inc., Canton, Mass.), and OrCel™ (Ortec International, Inc., New York, N.Y.), just to name a few.
Known, conventional materials suitable as a scaffold for cell growth while exhibiting acceptable absorption rates in the living body include natural and synthetic polymers such as collagen, gelatin, hyaluronic acid, pectin and cellulose derivatives. However, scaffolds manufactured by these materials have disadvantages such as relatively high tissue rejecting reactivity, weak mechanical properties and/or difficult to control their decomposition property. A short review on some of the improved materials and/or methods of producing skin substitutes developed by various research teams throughout the world is provided below.
U.S. Pat. No.: 6,599,323 B2 disclosed a biocompatible tissue implant, as well as methods for making and using such an implant. The tissue implant comprises one or more layers of bioabsorable polymeric foam having pores with an open cell structure. The foam component is reinforced with a material such as a mesh having a density in the range of about 12 to 80%. The foam component is formed from an elastomeric copolymer selected form the group consisting of ε-caprolactone-co-glycolide, ε-caprolactone-co-lactide, p-dioxanone (1,4-dioxan-2-one)-co-lactide, ε-caprolactone-co-p-dioxanone, p-dioxanone-co-trimethylene carbonate, trimethylene carbonate-co-glycolide, trimethylene carbonate-co-lactide, and combinations thereof. The mesh is formed from fibers made from a material selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, trimethylene carbonate, polyvinyl alcohol, copolymers thereof and combinations thereof.
U.S. Pat. No.: 6,733,530 is related to a skin material for engrafting onto a neodermis of a human patient, said material comprises a composite of: a biosynthetic substratum of an esterified hyaluronic acid, a layer of viable human dermal fibroblasts on an upper side of said biosynthetic substratum, and a layer of viable human keratinocytes over said dermal fibroblast upon said upper side of said biosynthetic substratum, said keratinocytes having been harvested from said patient.
U.S. Pat. No.: 6,974,679 B2 is related to a composite product forming a collagen support comprising at least one porous collagen layer covered on at least one side with an essentially compact collagen membrane consisting either of a collagen film prepared by drying a collagen gel, in air or in a gaseous fluid, or of a highly compressed collagen sponge.
U.S. Pat. No.: 6,946,143 B2 disclosed a biocompatible medical material and porous scaffold for use in tissue engineering, made from a biodegradable glycolide/ε-caprolactone copolymer with a molecular weight of about 10,000 daltons or more, and the molar ratio of glycolide:ε-caprolactone in the copolymer is about 4.0:6.0 to 6.0:4.0. The biodegradable polymer has low immunity, excellent mechanical properties and negligible toxicity, and is suitable for regeneration of soft tissues such as skin and blood vessel, and medical materials such as medical matrix and wound coverings.
U.S. Pat. No.: 6,991,652 B2 is related to a composite for use in a living subject, which comprises a biocompatible 3-dimensional construct comprising: a material selected from the group consisting of alginate, collagen, polylactide, polyethylene glycol, polycaprolactone, polycolide, polydioxanone, and derivatives and copolymers thereof and having a size greater than about 1.5 mm in diameter distributed within a carrier; said carrier comprising a gel matrix or viscous fluid, said gel matrix or said viscous fluid is selected from the group consisting of biodegradable materials and non-biodegradable materials, each having a viscosity of from 10 to 1000 cps; and cells disposed in said biocompatible 3-dimensional construct; wherein the 3-dimensional construct allows for the growth of cells disposed therein and for the ingrowth and attachment of surrounding tissue cells of the living subject.
U.S. Pat. No.: 6,846,675 B2 is related to an in vitro cultured skin substitutes with improved barrier function, which in some cases, is a result of improved culture conditions, while in other cases, is a result from genetic modification of keratinocytes. The skin substitutes thus prepared is useful for irritancy testing.
Inventors of this application had previously identified a biocomposite comprising collagen and PCL as a substrate for growth of skin cells (Dai et al., Biomaterials 25 (2004) 4263-4271; and Dai et al., Biochemical and Biophysical Research Communications 329 (2005) 905-908). For many years, collagen has been proven to be an irreplaceable substrate for the production of artificial skin substitutes containing living cells; however, collagen-based matrices are highly susceptible to bacterial and enzymatic attack and are generally unsuccessful when applied to chronic wounds heavily colonized with bacteria. Hence, there exist in this art a need to develop a biomaterial that is relatively inexpensive than any current biomaterials employed while exhibiting good mechanical strength, biological properties favorable to cell development and metabolism, and low susceptibility to bacterial and enzymatic degradation.